Cutting edge: IFN-gamma enables APC to promote memory Th17 and abate Th1 cell development.
Th1-derived IFN-gamma targets naive T cells and inhibits Th17 development. However, Th1, Th17, and memory but not naive T cells are colocalized in an inflammatory environment. To demonstrate the kinetic relationship between these T cell subsets, we investigated the role of IFN-gamma in regulating the development and balance between Th17 and Th1 in humans. We show that IFN-gamma stimulates B7-H1 expression on APC subsets and abates their Th1 polarization capacity in a B7-H1-dependent manner. Interestingly, IFN-gamma triggers APCs to produce IL-1 and IL-23 and enables them to induce memory Th17 expansion via IL-1 and IL-23 in a B7-H1-independent manner. We propose a novel dynamic between Th1 and Th17 in the course of inflammation as follows: Th1-mediated inflammation is attenuated by IFN-gamma-induced B7-H1 on APCs and is evolved toward Th17-mediated chronic inflammation by IFN-gamma-induced, APC-derived IL-1 and IL-23. Our study challenges the dogma that IFN-gamma suppresses Th17 and enhances Th1 development.
Kryczek
Ilona
I
Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Wei
Shuang
S
Gong
Wenrong
W
Shu
Xiaogong
X
Szeliga
Wojciech
W
Vatan
Linhua
L
Chen
Lieping
L
Wang
Guobin
G
Zou
Weiping
W
D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D015703:Antigens, CD / Q000502:physiology; D060890:B7-H1 Antigen; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D006131:Growth Inhibitors / Q000502:physiology*; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000502:physiology*; D007375:Interleukin-1 / Q000502:physiology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000502:physiology*; D053759:Interleukin-23 / Q000502:physiology; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D006131:Growth Inhibitors; D007375:Interleukin-1; D020381:Interleukin-17; D053759:Interleukin-23; D007371:Interferon-gamma